Israel and Iran moved closer to confrontation in Syria as rising tensions erupted into the most serious standoff between the sides since the Syrian civil war began seven years ago.

The Israeli military on Saturday said it struck 12 targets in Syria, including four belonging to Iran, in a “large-scale attack” after an Iranian drone penetrated its airspace. An F-16 fighter plane crashed in northern Israel after coming under fire from Syrian anti-aircraft missiles, and the pilots were hospitalized with moderate to severe injuries.

Saturday’s confrontation comes amid Israeli warnings that it won’t let Syria become an Iranian base or a conduit for weapons bound for Iran-backed Hezbollah militants in Lebanon. Iran and allied militias have fought alongside government troops against rebels and Islamist factions in the Syrian war.